Add-On Celiac, IBS, and Crohn's Assay (CICA)

Tissue transglutaminase is an enzyme that deamidates gliadin peptides in the intestinal lamina propria. In coeliac disease, these modified peptides bind HLA-DQ2 or HLA-DQ8 on antigen-presenting cells, triggering a T-cell response and production of IgG and IgA antibodies against tissue transglutaminase itself. IgG anti-tTG antibodies are measured primarily in patients with selective IgA deficiency, who cannot mount an IgA anti-tTG response.

IgG anti-tTG is a second-line coeliac serology when IgA testing is unavailable or the patient has confirmed IgA deficiency. Its sensitivity and specificity are lower than IgA anti-tTG, so it supplements rather than replaces standard serology in most cases.

IgA antibodies to tissue transglutaminase are the dominant immunoglobulin class in the coeliac immune response. They are produced by plasma cells in the intestinal mucosa and appear in serum when gluten exposure is ongoing. IgA anti-tTG correlates closely with the degree of villous atrophy and falls on a gluten-free diet, making it the cornerstone of both diagnosis and monitoring.

IgA anti-tTG is the single most sensitive and specific serological marker of coeliac disease in immunocompetent patients. A strongly positive result in a patient with compatible symptoms and HLA-DQ2 or HLA-DQ8 may permit diagnosis without initial biopsy in selected paediatric cases, though biopsy remains the reference standard in adults.

Saccharomyces cerevisiae is baker's and brewer's yeast; antibodies to its cell-wall mannans are markers of an aberrant mucosal immune response to commensal and dietary fungi. ASCA IgG and IgA appear more frequently in Crohn's disease than in ulcerative colitis or healthy controls, though the antigenic trigger and pathogenic role remain incompletely understood.

ASCA positivity (IgG or IgA, or both) is seen in roughly half of Crohn's disease patients and is more specific for Crohn's than for ulcerative colitis. When combined with perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) — typically positive in ulcerative colitis and negative in Crohn's — serology can support differentiation of inflammatory bowel disease subtypes, though endoscopy and histology remain definitive.

Like ASCA IgG, ASCA IgA reflects mucosal immune recognition of yeast mannans. The two isotypes often appear together, and dual positivity strengthens the association with Crohn's disease. IgA isotypes are particularly relevant at mucosal surfaces, where secretory IgA dominates local immunity.

ASCA IgA adds incremental diagnostic value when interpreted alongside ASCA IgG. Dual positivity (both IgG and IgA) has higher specificity for Crohn's disease than either alone, and the combination with negative pANCA further favours Crohn's over ulcerative colitis.

CBir1 is a bacterial flagellin derived from commensal gut flora. Antibodies to CBir1 are markers of a loss of tolerance to flagellated intestinal bacteria and are seen predominantly in Crohn's disease, correlating with complicated, fibrostenotic, and perforating phenotypes. The presence of anti-CBir1 antibodies implies that bacterial antigens drive part of the mucosal immune response in susceptible individuals.

Anti-CBir1 is not a diagnostic test for Crohn's disease on its own, but it adds prognostic information: positivity is associated with more aggressive disease, higher risk of surgical intervention, and complicated behaviour. It may help practitioners identify patients who warrant closer monitoring or earlier escalation of therapy.